Cerebellar Hemangioblastoma Associated With a Vascular Malformation: A Case Report Treated With Surgery and Radiosurgery.

Hemangioblastoma is well known as an essentially benign cystic and/or solid tumor classified WHO grade I, mainly originated in the posterior fossa. One of the characteristics of this tumor is very rich vasculature in and around the tumor. We have encountered a case of hemangioblastoma in association with a vascular anomaly near the tumor, though they were located separately by the tentorium. A vascular anomaly with arteriovenous (AV) shunting flow in the left occipital lobe was verified at angiography, which received a blood supply from left occipital artery and drained to occipital cortical veins. Successful removal of the cerebellar tumor and pathological diagnosis of hemangioblastoma was made. The second angiography in our hospital demonstrated the same vascular anomaly above the tentorium with feeding artery of posterior cerebral artery, a small nidus, and cortical draining veins, which were less obviously stained. Only the arteriovenous malformation (AVM) nidus in sigmoid vein was targeted for radiosurgery and 20 Gy at the margin was delivered. Since AV shunting was less remarkable on the second angiography than that on the first angiography may be because of a decreased vascular supply to the supratentorial AVM after surgical resection of the infratentorial hemangioblastoma and might indicate an indirect connection between the two lesions.

Neuroendocrine Carcinoma of Uterine Cervix: Stereotactic Radiotherapy for Brain Metastasis and Stereotactic Body Radiotherapy for Renal and Pancreatic Metastases.

A case of cervical neuroendocrine carcinoma (NEC) of the uterine cervix (NECUC) was presented. After total hysterectomy with bilateral salpingo-oophorectomy and adjuvant chemotherapy, a left renal tumor and a pancreatic lesion developed and were both diagnosed on pathological examination as metastases from NEC. In addition, a brainstem metastasis causing neurologic signs developed. The brain lesion was treated by stereotactic radiotherapy (SRT) and the renal and pancreatic lesions by stereotactic body radiotherapy (SBRT). Despite control of the renal and pancreatic lesions, multiple small lung metastases developed later. Recurrence and newly developed brain metastases were treated by repeat stereotactic radiosurgery (SRS)/SRT successfully. Chemotherapy was continued and controlled the lung metastases until three and a half years after the initial operation of the uterus.

Stereotactic Radiosurgery and Stereotactic Radiotherapy for Malignant Skull Base Tumors.

The role of stereotactic radiosurgery/stereotactic radiotherapy (SRS/SRT) for malignant skull base tumors was summarized and discussed. The treatment of skull base tumors remains challenging. Their total resection is often difficult. SRS/SRT is one useful treatment option for residual or recurrent tumors after surgical resection in cases of primary skull base tumors. If skull base metastasis and skull base invasion are relatively localized, they can be candidates for SRS/SRT. Low rates of cervical lymph node involvement in early-stage (N0M0, no lymph node involvement or distant metastasis) nasal and paranasal carcinomas (NpNCa) and external auditory canal carcinomas (EACCa) have been reported in the literature. Such cases might be good candidates for SRS/SRT as the initial therapy. We previously reported the results of SRS/SRT for various malignant extra-axial skull base tumors. In addition, treatment results of early-stage head and neck carcinomas were summarized. Those of our data and those of other reported series were reviewed here to clarify the usefulness of SRS/SRT for malignant extra-axial skull base tumors.

Radiosurgery for Patients with More Than Ten Brain Metastases.

Purpose In this article, we report on Gamma Knife radiosurgery performed on patients with more than 10 brain metastases. Although the standard treatment for multiple brain metastases is currently believed to be whole-brain irradiation, many patients are averse to it due to the potential for serious complications such as cognitive impairment. Cases and Methods Here, 70 cases of Gamma Knife radiosurgery for metastatic foci originating from various primary cancer are reviewed. Several different treatment protocols were selected: (1) single session, (2) two or three consecutive sessions, (3) fractionated irradiation for large tumor and stereotactic radiosurgery (SRS) for small ones, and (4) salvage treatment for recurrent tumors after whole-brain irradiation. Results Despite the long beam-on-time (BOT) necessary for Gamma Knife radiosurgery and unavoidable spillage irradiation to the entire brain, all the treatments were completed without any major difficulties. Conclusion SRS or radiotherapy might be a treatment choice for patients with more than 10 brain metastases. However, the very long treatment time and big spillage irradiation to the entire brain warrants that large metastatic foci should be removed before or after radiosurgery.

Salvage gamma knife radiosurgery for active brain metastases from small-cell lung cancer after whole-brain radiation therapy: a retrospective multi-institutional study (JLGK1701).

PURPOSE: To evaluate the efficacy of gamma knife radiosurgery (GKS) for brain metastases (BMs) from small-cell lung cancer after whole-brain radiotherapy (WBRT). METHODS: We retrospectively analyzed the usefulness and safety of GKS in 163 patients from 15 institutions with 1-10 active BMs after WBRT. The usefulness and safety of GKS were evaluated using statistical methods. RESULTS: The median age was 66 years, and 79.1% of patients were men. The median number and largest diameter of BM were 2.0 and 1.4 cm, respectively. WBRT was administered prophylactically in 46.6% of patients. The median overall survival (OS) was 9.3 months, and the neurologic mortality was 20.0%. Crude incidences of local control failure and new lesion appearance were 36.6% and 64.9%, respectively. A BM diameter ≥ 1.0 cm was a significant risk factor for local progression (hazard ratio [HR] 2.556, P = 0.039) and neurologic death (HR 4.940, P = 0.031). Leukoencephalopathy at the final follow-up was more prevalent in the therapeutic WBRT group than in the prophylactic group (P = 0.019). The symptom improvement rate was 61.3%, and neurological function was preserved for a median of 7.6 months. Therapeutic WBRT was not a significant risk factor for OS, neurological death, local control, or functional deterioration (P = 0.273, 0.490, 0.779, and 0.560, respectively). Symptomatic radiation-related adverse effects occurred in 7.4% of patients. CONCLUSIONS: GKS can safely preserve neurological function and prevent neurologic death in patients with 1-10 small, active BMs after prophylactic and therapeutic WBRT.

One-Day Two-Fraction Radiosurgery for Brain Metastases Using Gamma Knife.

OBJECTIVE: We aimed to evaluate the feasibility of a one-day two-fraction Gamma Knife radiosurgery (GKRS) for brain metastases. CASES AND METHODS: Ten cases with ten brain metastases (four cases of lung adenocarcinoma, one small cell lung carcinoma (SCLC), two renal cell carcinoma, one breast cancer, one esophageal carcinoma, and one bile duct carcinoma) were treated by one-day two-fraction (with an interval of more than six hours) GKRS under rigid skull frame fixation. Of the ten brain metastases, five lesions were in the frontal lobe, one in temporal, one in occipital, and three in the cerebellar hemisphere. The mean planning target volume (PTV) of the ten brain tumors was 7.8 ml (median, 8.0; range, 3.8 - 11.8). The ten targets of the mean prescription isodose volume (PIV) of 10.1 ml (median, 10.1; range, 4.4 - 15.9) were treated with a mean margin dose of 20.4 Gy (median, 20.5; range, 16.4 - 22) in two fractions. In five cases, other small brain metastases (one to seven tumors) were also treated simultaneously in a single fraction GKRS. The indication of two-fraction radiosurgery was large lesion size in eight, retreatment in three, the proximity of the motor area in three, and pre-existing perifocal edema symptom of dysarthria in two, nausea and vomiting in one, and dementia in one. RESULTS: Eight cases were alive at the end of the follow-up period of one to nine months (median, 6). One patient with SCLC died four and a half months after GKRS, from aggressive regrowth of the treated frontal lesion after transient marked shrinkage. Another patient died four months after GKRS due to the progression of other brain tumors treated by single fraction GKRS at the same time. In nine of 10 cases, the size of the treated tumors was controlled until the end of the follow-up period or the patient's death. In two cases, an additional GKRS was performed for newly developed brain metastases at distant locations at six months and five months after one-day two-fraction GKRS, respectively, and controlled at the end of the follow-up period. CONCLUSIONS: A relatively high dose may be safely delivered to large lesions, to those close to the important structures, or those with perifocal edema by one-day two-fraction radiosurgery. Local control was good except for a relapsed SCLC metastasis case. Evaluation in more cases with a longer follow-up period is necessary to determine definite indications and optimal prescription doses.

Stereotactic Radiotherapy with Fractionation for the Lesions in and Around the Brainstem and Optic Nerve.

Purpose Among the components of the central nervous system, the optic nerve and the brainstem are considered to be the eloquent structures that are sensitive to stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). SRS or SRT with fractionation in areas adjacent to these tissues is both promising and challenging. Materials and methods To clarify the precise dose distribution achievable with fractionation in and around the optic nerve and brainstem, theoretical simulations were performed, based on the biological effective dose (BED). Results These simulations clearly showed that the doses to the optic nerve and brainstem can be adjusted using fractionation, meaning that the prescribed doses to the surrounding brain tissue can be reduced. Conversely doses to the lesions themselves can be increased by fractionation, while maintaining a stable dose to normal optic nerve and brainstem tissue.

Radiosurgery for Symptomatic Cavernous Malformation in the Brainstem: Two Difficult Cases with Large and Multiple Lesions.

It is well known that cavernous malformations become much more hemorrhagic after the initial hemorrhage and that brainstem lesions are more dangerous than the lesions in the supratentorial location. It is very difficult to handle symptomatic cavernous malformations associated with repetitive hemorrhages in the brainstem. Patients may be suffering from brainstem syndromes such as hemiparesis, hemisensory disturbance, ataxia, and disturbed ocular movement. We have encountered two such difficult cases, one is very large and the other is multiple and familiar, accompanying repetitive brainstem hemorrhages. Since microsurgery seems to be very difficult and hazardous, these two cases were treated with radiosurgery after several hemorrhages.

Radiosurgery for Epidermoid Tumors: Dramatic Pain Relief from Trigeminal Neuralgia.

Purpose  The purpose of this study is to discuss the long-term effects of radiosurgery for epidermoid tumors, including the symptoms of trigeminal neuralgia and/or facial spasm, which we have originally reported before. Background Intracranial epidermoids are slow-growing tumors that can become symptomatic once they develop into large tumors. The mainstay of the treatment is surgery. However, eradicating the whole tumor is often difficult and some tumors may recur. In addition to their mass effects on the brain, these tumors are often associated with hyperactive nerve dysfunction syndromes such as trigeminal neuralgia, glossopharyngeal neuralgia, and/or facial spasm. Cases and methods  We report 13 cases of epidermoid tumors, 12 of which were located in the cerebellopontine angle (CPA), which were treated using 14 radiosurgery procedures. The inclusion criteria for radiosurgery were the presence of well-localized small tumors and/or severe associated neuralgia or facial spasms. The mean target volume ranged from 0.17 to 9.5 cm3 with a mean of 2.85 cm3. The lesions were treated with a mean maximum and a marginal dose of 28.2 Gy and 14.2 Gy, respectively. Results Among the 14 gamma knife procedures that were performed in 13 patients, dose planning to ensure total and partial coverage for relief from hyperactive cranial nerve dysfunction (HCND) was performed. Six cases were totally and another eight were partially covered at the dose planning. The irradiated tumors showed a minor decrease or no remarkable changes during a mean follow-up period of 86.1 months. Tumor progression requiring a second surgery was seen in two cases. The trigeminal neuralgias either improved or disappeared soon after the procedure, enabling the discontinuation of the medication. Conclusion  Radiosurgery led to a dramatic improvement in HCND. In fact, the immediate cure of neuralgia after the radiosurgery was observed in several cases, even after partial coverage with radiosurgery. The interface between the tumor and the nerve was the main target. The definite mechanisms for this favorable outcome have not been verified yet, but the functional modulation by the radiosurgery could be one. Electrophysiological alteration at the interface between the tumor and nerve has been considered. When the tumors were totally covered with radiosurgery, persistent tumor control was expected. Sufficient tumor control is possible if the tumor can be covered entirely with radiosurgery. Functional modulation of trigeminal neuralgia and facial spasms can also be attained even by partial dose planning for the nerve-tumor interface.

Treatment Results of Gamma Knife Radiosurgery for Central Neurocytoma: Report of a Japanese Multi-Institutional Cooperative Study.

OBJECTIVE: Central neurocytoma (CN) is a rare benign neuronal tumor, and a limited number of reports have described the usefulness of radiosurgery for a relatively large group of patients. We evaluated the effectiveness and outcomes of Gamma Knife radiosurgery (GKS) for CN in a Japanese multi-institutional study. METHODS: We performed retrospective analysis of 36 patients with CN who were treated with GKS in 12 institutes in Japan. All patients underwent surgery before GKS. The median tumor volume at GKS was 4.9 mL (range, 0.07-23.4 mL), and the median radiation dose prescribed to the tumor margin was 15 Gy (range, 10-20 Gy). The median follow-up period was 54.5 months (range, 3-180 months). RESULTS: The local tumor progression-free survival rates at 5 and 10 years were 94% and 86%, respectively. Three patients developed distant dissemination 16-90 months later. Overall progression-free survival was unrelated to the prescribed dose (<15 Gy vs. ≥15 Gy, P = 0.62), tumor size (<6 mL vs. ≥6 mL, P = 0.46), gender (P = 0.36), age (<30 vs. ≥30 years, P = 0.37), target of GKS (residual vs. recurrence, P = 0.90), and type of enhancement (homogeneous vs. inhomogeneous, P = 0.19). Two permanent complications occurred with 1 intratumoral hemorrhage and 1 radiation injury. CONCLUSIONS: GKS is effective for CN because of its high rate of long-term local tumor control. GKS may have a potential role as a primary treatment for asymptomatic, relatively small tumors in the absence of hydrocephalus without surgical resection.

Gamma Knife surgery for patients with jugular foramen schwannomas: a multiinstitutional retrospective study in Japan.

OBJECTIVE This study aimed to explore the efficacy and safety of stereotactic radiosurgery in patients with jugular foramen schwannomas (JFSs). METHODS This study was a multiinstitutional retrospective analysis of 117 patients with JFSs who were treated with Gamma Knife surgery (GKS) at 18 medical centers of the Japan Leksell Gamma Knife Society. The median age of the patients was 53 years. Fifty-six patients underwent GKS as their initial treatment, while 61 patients had previously undergone resection. At the time of GKS, 46 patients (39%) had hoarseness, 45 (38%) had hearing disturbances, and 43 (36%) had swallowing disturbances. Eighty-five tumors (73%) were solid, and 32 (27%) had cystic components. The median tumor volume was 4.9 cm3, and the median prescription dose administered to the tumor margin was 12 Gy. Five patients were treated with fractionated GKS and maximum and marginal doses of 42 and 21 Gy, respectively, using a 3-fraction schedule. RESULTS The median follow-up period was 52 months. The last follow-up images showed partial remission in 62 patients (53%), stable tumors in 42 patients (36%), and tumor progression in 13 patients (11%). The actuarial 3- and 5-year progression-free survival (PFS) rates were 91% and 89%, respectively. The multivariate analysis showed that pre-GKS brainstem edema and dumbbell-shaped tumors significantly affected PFS. During the follow-up period, 20 patients (17%) developed some degree of symptomatic deterioration. This condition was transient in 12 (10%) of these patients and persistent in 8 patients (7%). The cause of the persistent deterioration was tumor progression in 4 patients (3%) and adverse radiation effects in 4 patients (3%), including 2 patients with hearing deterioration, 1 patient with swallowing disturbance, and 1 patient with hearing deterioration and hypoglossal nerve palsy. However, the preexisting hoarseness and swallowing disturbances improved in 66% and 63% of the patients, respectively. CONCLUSIONS GKS resulted in good tumor control in patients with either primary or residual JFSs. Although some patients experienced some degree of symptomatic deterioration after treatment, persistent adverse radiation effects were seen in only 3% of the entire series at the last follow-up. Lower cranial nerve deficits were extremely rare adverse radiation effects, and preexisting hoarseness and swallowing disturbances improved in two-thirds of patients. These results indicated that GKS was a safe and reasonable alternative to surgical resection in selected patients with JFSs.

Gamma Knife surgery for patients with facial nerve schwannomas: a multiinstitutional retrospective study in Japan.

OBJECTIVE: The aim of this study was to explore the efficacy and safety of stereotactic radiosurgery for patients with facial nerve schwannomas (FNSs). METHODS: This study was a multiinstitutional retrospective analysis of 42 patients with FNSs treated with Gamma Knife surgery (GKS) at 1 of 10 medical centers of the Japan Leksell Gamma Knife Society (JLGK1301). The median age of the patients was 50 years. Twenty-nine patients underwent GKS as the initial treatment, and 13 patients had previously undergone surgery. At the time of the GKS, 33 (79%) patients had some degree of facial palsy, and 21 (50%) did not retain serviceable hearing. Thirty-five (83%) tumors were solid, and 7 (17%) had cystic components. The median tumor volume was 2.5 cm(3), and the median prescription dose to the tumor margin was 12 Gy. RESULTS: The median follow-up period was 48 months. The last follow-up images showed partial remission in 23 patients and stable tumors in 19 patients. Only 1 patient experienced tumor progression at 60 months, but repeat GKS led to tumor shrinkage. The actuarial 3- and 5-year progression-free survival rates were 100% and 92%, respectively. During the follow-up period, 8 patients presented with newly developed or worsened preexisting facial palsy. The condition was transient in 3 of these patients. At the last clinical follow-up, facial nerve function improved in 8 (19%) patients, remained stable in 29 (69%), and worsened in 5 (12%; House-Brackmann Grade III in 4 patients, Grade IV in 1 patient). With respect to hearing function, 18 (90%) of 20 evaluated patients with a pure tone average of ≤ 50 dB before treatment retained serviceable hearing. CONCLUSIONS: GKS is a safe and effective treatment option for patients with either primary or residual FNSs. All patients, including 1 patient who required repeat GKS, achieved good tumor control at the last follow-up. The incidence of newly developed or worsened preexisting facial palsy was 12% at the last clinical follow-up. In addition, the risk of hearing deterioration as an adverse effect of radiation was low. These results suggest that GKS is a safe alternative to resection.

Radiosurgery for symptomatic cavernous malformations: A multi-institutional retrospective study in Japan.

BACKGROUND: A group study for symptomatic cavernous malformation (CM) treated with gamma knife (GK) surgery was performed. METHODS: A total of 298 cases collected from 23 GK centers across Japan were included. Hemorrhage was the most common manifestation, followed by seizures and neurological deficits. Most of the lesions were located in the brainstem and basal ganglia, followed by the cerebral or cerebellar hemispheres. The CMs, which had a mean diameter of 14.8 mm, were treated using GK surgery with a mean marginal dose of 14.6 Gy. RESULTS: In terms of hemorrhage-free survival (HFS), a marked dissociation was confirmed between the hemorrhage and seizure groups, while no obvious difference was noted between sexes. Superficial CMs located in cerebellum or lobar regions responded to the treatment better than deeply located CMs in the basal ganglia or brainstem. No significant difference of dose-dependent response was seen for three different ranges of marginal dose: Less than 15 Gy, between 15 and 20 Gy, and more than 20 Gy. Complications were more frequent after a marginal dose of over 15 Gy and in patients with lesions more than 15 mm in diameter. The rates of annual hemorrhage were estimated to be 7.4% during the first 2 years after radiosurgery and 2.8% thereafter. The overall hemorrhage rate after radiosurgery was 4.4%/year/patient. CONCLUSION: The risk of hemorrhage is considerably reduced after GK treatment. The HFS as well as annual hemorrhage rate after GK treatment was apparently superior to that after conservative treatment for symptomatic CMs. To optimize the success of GK treatment, it is important to reduce the incidence of complications.

Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study.

BACKGROUND: We aimed to examine whether stereotactic radiosurgery without whole-brain radiotherapy (WBRT) as the initial treatment for patients with five to ten brain metastases is non-inferior to that for patients with two to four brain metastases in terms of overall survival. METHODS: This prospective observational study enrolled patients with one to ten newly diagnosed brain metastases (largest tumour <10 mL in volume and <3 cm in longest diameter; total cumulative volume ≤15 mL) and a Karnofsky performance status score of 70 or higher from 23 facilities in Japan. Standard stereotactic radiosurgery procedures were used in all patients; tumour volumes smaller than 4 mL were irradiated with 22 Gy at the lesion periphery and those that were 4-10 mL with 20 Gy. The primary endpoint was overall survival, for which the non-inferiority margin for the comparison of outcomes in patients with two to four brain metastases with those of patients with five to ten brain metastases was set as the value of the upper 95% CI for a hazard ratio (HR) of 1·30, and all data were analysed by intention to treat. The study was finalised on Dec 31, 2012, for analysis of the primary endpoint; however, monitoring of stereotactic radiosurgery-induced complications and neurocognitive function assessment will continue for the censored subset until the end of 2014. This study is registered with the University Medical Information Network Clinical Trial Registry, number 000001812. FINDINGS: We enrolled 1194 eligible patients between March 1, 2009, and Feb 15, 2012. Median overall survival after stereotactic radiosurgery was 13·9 months [95% CI 12·0-15·6] in the 455 patients with one tumour, 10·8 months [9·4-12·4] in the 531 patients with two to four tumours, and 10·8 months [9·1-12·7] in the 208 patients with five to ten tumours. Overall survival did not differ between the patients with two to four tumours and those with five to ten (HR 0·97, 95% CI 0·81-1·18 [less than non-inferiority margin], p=0·78; pnon-inferiority<0·0001). Stereotactic radiosurgery-induced adverse events occurred in 101 (8%) patients; nine (2%) patients with one tumour had one or more grade 3-4 event compared with 13 (2%) patients with two to four tumours and six (3%) patients with five to ten tumours. The proportion of patients who had one or more treatment-related adverse event of any grade did not differ significantly between the two groups of patients with multiple tumours (50 [9%] patients with two to four tumours vs 18 [9%] with five to ten; p=0·89). Four patients died, mainly of complications relating to stereotactic radiosurgery (two with one tumour and one each in the other two groups). INTERPRETATION: Our results suggest that stereotactic radiosurgery without WBRT in patients with five to ten brain metastases is non-inferior to that in patients with two to four brain metastases. Considering the minimal invasiveness of stereotactic radiosurgery and the fewer side-effects than with WBRT, stereotactic radiosurgery might be a suitable alternative for patients with up to ten brain metastases. FUNDING: Japan Brain Foundation.

Long-term results for trigeminal schwannomas treated with gamma knife surgery.

PURPOSE: Surgical resection is considered the desirable curative treatment for trigeminal schwannomas. However, complete resection without any complications remains challenging. During the last several decades, stereotactic radiosurgery (SRS) has emerged as a minimally invasive treatment modality. Information regarding long-term outcomes of SRS for patients harboring trigeminal schwannomas is limited because of the rarity of this tumor. The aim of this study was to evaluate long-term tumor control and functional outcomes in patients harboring trigeminal schwannomas treated with SRS, specifically with gamma knife surgery (GKS). METHODS AND MATERIALS: Fifty-three patients harboring trigeminal schwannomas treated with GKS were evaluated. Of these, 2 patients (4%) had partial irradiation of the tumor, and 34 patients (64%) underwent GKS as the initial treatment. The median tumor volume was 6.0 cm(3). The median maximum and marginal doses were 28 Gy and 14 Gy, respectively. RESULTS: The median follow-up period was 98 months. On the last follow-up image, 7 patients (13%) had tumor enlargement, including the 2 patients who had partial treatment. Excluding the 2 patients who had partial treatment, the actuarial 5- and 10-year progression-free survival (PFS) rates were 90% and 82%, respectively. Patients with tumors compressing the brainstem with deviation of the fourth ventricle had significantly lower PFS rates. If those patients with tumors compressing the brainstem with deviation of the fourth ventricle are excluded, the actuarial 5- and 10-year PFS rates increased to 95% and 90%, respectively. Ten percent of patients had worsened facial numbness or pain in spite of no tumor progression, indicating adverse radiation effect. CONCLUSIONS: GKS can be an acceptable alternative to surgical resection in patients with trigeminal schwannomas. However, large tumors that compress the brainstem with deviation of the fourth ventricle should be surgically removed first and then treated with GKS when necessary.

Long-term safety and efficacy of stereotactic radiosurgery for vestibular schwannomas: evaluation of 440 patients more than 10 years after treatment with Gamma Knife surgery.

Object Little is known about long-term outcomes, including tumor control and adverse radiation effects, in patients harboring vestibular schwannomas (VSs) treated with stereotactic radiosurgery > 10 years previously. The aim of this study was to confirm whether Gamma Knife surgery (GKS) for VSs continues to be safe and effective > 10 years after treatment. Methods A total of 440 patients with VS (including neurofibromatosis Type 2) treated with GKS between May 1991 and December 2000 were evaluable. Of these, 347 patients (79%) underwent GKS as an initial treatment and 93 (21%) had undergone prior resection. Three hundred fifty-eight patients (81%) had a solid tumor and 82 (19%) had a cystic tumor. The median tumor volume was 2.8 cm(3) and the median marginal dose was 12.8 Gy. Results The median follow-up period was 12.5 years. The actuarial 5- and ≥ 10-year progression-free survival was 93% and 92%, respectively. No patient developed treatment failure > 10 years after treatment. According to multivariate analysis, significant factors related to worse progression-free survival included brainstem compression with a deviation of the fourth ventricle (p < 0.0001), marginal dose ≤ 13 Gy (p = 0.01), prior treatment (p = 0.02), and female sex (p = 0.02). Of 287 patients treated at a recent optimum dose of ≤ 13 Gy, 3 (1%) developed facial palsy, including 2 with transient palsy and 1 with persistent palsy after a second GKS, and 3 (1%) developed facial numbness, including 2 with transient and 1 with persistent facial numbness. The actuarial 10-year facial nerve preservation rate was 97% in the high marginal dose group (> 13 Gy) and 100% in the low marginal dose group (≤ 13 Gy). Ten patients (2.3%) developed delayed cyst formation. One patient alone developed malignant transformation, indicating an incidence of 0.3%. Conclusions In this study GKS was a safe and effective treatment for the majority of patients followed > 10 years after treatment. Special attention should be paid to cyst formation and malignant transformation as late adverse radiation effects, although they appeared to be rare. However, it is necessary to collect further long-term follow-up data before making conclusions about the long-term safety and efficacy of GKS, especially for young patients with VSs.

Moyamoya syndrome associated with γ knife surgery for cerebral arteriovenous malformation: case report.

A 30-year-old female developed moyamoya syndrome after gamma knife surgery (GKS) for cerebral arteriovenous malformation (AVM), and was treated with bypass surgery. She suffered from flittering scotoma, right transient hemianopsia, and headache for 1 year. Cerebral angiography revealed a Spetzler-Martin grade III AVM located in the left occipital lobe. After staged embolization, GKS was performed with a minimum dose of 20 Gy to the periphery of the nidus at the 50% isodose level of the maximum target dose. Gradual nidus regression was achieved, and the clinical symptoms disappeared completely. However, at 30 months after GKS, the patient suffered transient ischemic attack. Cerebral angiography showed left middle cerebral artery occlusion with moyamoya vessels. The patient underwent direct and indirect bypass surgery. After surgery, the patient was free from ischemic symptoms. Chronic inflammation and long-term changes in expression of cytokines and growth factors after GKS may have triggered this case.

Factors associated with hearing preservation after Gamma Knife surgery for vestibular schwannomas in patients who retain serviceable hearing.

OBJECT: Gamma Knife surgery (GKS) has been a safe and effective treatment for small- to medium-sized vestibular schwannomas (VSs) over relatively long-term outcomes. However, even with recent radiosurgical techniques, hearing results following GKS remain unsatisfactory. The purpose of this study was to evaluate the hearing preservation rate as well as factors related to hearing preservation in patients with VSs and serviceable hearing who were treated with GKS. METHODS: Among patients with Gardner-Robertson (GR) Class I or II serviceable hearing and VSs treated with GKS between 1991 and 2009, 117 were evaluable via periodic MR imaging and audiometry. RESULTS: The median age at the time of GKS was 52 years. Four patients (3%) had undergone prior surgery. Fifty-six patients (48%) had GR Class I hearing and 61 (52%) had GR Class II hearing at the time of GKS. The median tumor volume was 1.9 cm(3). The median maximum and tumor margin radiation doses were 24 and 12 Gy, respectively. The median follow-up periods for MR imaging and audiometry were 74 and 38 months, respectively. The overall tumor control rate was 97.5%. Actuarial 3-, 5-, and 8-year hearing preservation rates were 55%, 43%, and 34%, respectively. On multivariate analysis, GR hearing class at the time of GKS and the mean cochlear dose affected hearing preservation significantly. In a limited number of patients who were treated using the most recent dose planning techniques and who had GR Class I hearing before treatment, the 3- and 5-year hearing preservation rates increased to 80% and 70%, respectively. CONCLUSIONS: For the majority of patients with small- to medium-sized VSs, GKS was an effective and reasonable alternative to resection with satisfactory long-term tumor control. Factors related to hearing preservation included a GR Class I hearing pre-GKS and a lower mean cochlear radiation dose. To retain serviceable hearing, it is important to apply GKS treatment while patients retain GR Class I hearing.

Gamma Knife surgery for convexity, parasagittal, and falcine meningiomas.

OBJECT: The aim of this study was to evaluate the outcomes in patients with convexity, parasagittal, or falcine meningiomas treated using Gamma Knife surgery (GKS) and to determine management strategy considering a risk of radiation-induced edema. METHODS: One hundred twelve patients who harbored 125 convexity, parasagittal, or falcine meningiomas were assessed. Forty-six patients underwent GKS as the initial treatment. The median tumor diameter was 25 mm, and median tumor volume was 8 cm(3). The median maximum and margin doses were 30 and 16 Gy, respectively. RESULTS: The median follow-up period was 72 months. The actuarial 5- and 10-year progression-free survival rates were 78% and 55%, respectively. The actuarial 5- and 10-year local tumor control rates were 87% and 71%, respectively. Of 29 tumors that developed postradiosurgical edema, 7 were symptomatic. The actuarial symptomatic radiation-induced edema rate was 7%. The incidence of this complication was significantly higher in patients who underwent GKS as the initial treatment. Six of 46 patients for whom GKS was the initial treatment had preradiosurgical edema. Of these 6 patients, 4 developed severe panhemispheric edema after GKS (2 patients with parasagittal tumors, 1 with a falx tumor, and 1 with a convexity tumor). CONCLUSIONS: Gamma Knife surgery is an effective treatment for convexity, parasagittal, and falcine meningiomas as the initial or adjuvant treatment. However, GKS should be restricted to small- to medium-sized tumors, particularly in patients with primary tumors, because radiation-induced edema is more common in convexity, parasagittal, and falcine meningiomas than skull base meningiomas.

Tolerance of the optic apparatus in single-fraction irradiation using stereotactic radiosurgery: evaluation in 100 patients with craniopharyngioma.

OBJECTIVE: To determine the limiting dose to the optic apparatus in single-fraction irradiation in patients with craniopharyngioma treated with gamma knife radiosurgery (GKRS). METHODS: One hundred patients with 109 craniopharyngiomas treated with GKRS were evaluated with a median follow-up period of 68 months. Tumor volume varied from 0.1 to 36.0 (median, 3.3) cm. Marginal doses varied from 10 to 18 (median, 11.4) Gy. Maximum dose to any part of the optic apparatus varied from 2 to 18 (median, 10) Gy. RESULTS: The actuarial 5- and 10-year overall rates of survival of tumor progression after GKRS were 93% and 88%, respectively. Similarly, the actuarial 5- and 10-year progression-free survival rates were 62% and 52%, respectively. Among 94 patients in whom visual function was evaluable after GKRS, only 3 patients developed radiation-induced optic neuropathy, indicating an overall Kaplan-Meier radiation-induced optic neuropathy rate of 5%. Of these patients, 2 received 15 Gy or greater to the optic apparatus. Another patient who received 8 Gy or less had undergone previous fractionated radiation therapy with a biologically effective dose of 60 Gy. CONCLUSION: The optic apparatus seems to be more tolerant of irradiation than previously thought. Careful dose planning is essential, particularly in patients who underwent prior external beam radiation therapy.